# Project 3: Tumor Antigen Reactive Donor T Cell Immunotherapy

> **NIH NIH P01** · STANFORD UNIVERSITY · 2023 · $334,901

## Abstract

Project 3: Project Summary/Abstract
The object of the proposed studies is to determine whether tumor antigen vaccination of donors of MHC matched
hematopoietic cell transplants (HCT) can increase graft-versus-tumor (GVT) activity without increasing graft-
versus-host disease (GVHD) in both pre-clinical and clinical studies. In the case of B cell lymphomas, we will
use vaccination with idiotype peptides derived from the B-cell receptor (BCR) CDR3 region to immunize against
the tumors. In the case of myeloid leukemia, we will use vaccination with the WT-1 peptide that is an
overexpressed leukemia tumor antigen. Mouse and human recipients with B cell lymphoma will be conditioned
with total lymphoid irradiation and anti-thymocyte antibodies (an acute GVHD protective regimen), and mixed
chimeras will receive phenotypic CD8+ memory T (TM) cell donor lymphocyte infusions (DLI) that mediate GVT
without GVHD from idiotype immunized donors. Sorted CD8+ TM cells express the CD8+CD44hi phenotype in
mice, and CD8+CD45R0+CD45RA- phenotype in humans. It is also expected that the DLI will induce conversion
from mixed to complete chimerism, and that the tumor antigen immunized TM cell DLI will mediate potent GVT
activity as compared to the nonimmunized TM cell DLI. Booster vaccinations of recipients is expected to increase
anti-tumor activity even further. GVHD will be minimized in myeloid leukemia transplant recipients given
myeloablative conditioning by using T cell depleted (TCD) CD34+ selected grafts combined with donor CD8+ TM
cells. The infusion of the latter cells is expected to improve immune reconstitution and GVT activity as compared
to TCD CD34+ selected grafts alone. In summary, we will use strategies developed in our laboratory to prevent
GVHD, and tumor antigen immunization to increase GVT activity such that overall and event-free survival is
increased in the proposed preclinical and clinical studies.

## Key facts

- **NIH application ID:** 10700007
- **Project number:** 5P01CA049605-33
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Robert Lowsky
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $334,901
- **Award type:** 5
- **Project period:** 1997-05-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10700007

## Citation

> US National Institutes of Health, RePORTER application 10700007, Project 3: Tumor Antigen Reactive Donor T Cell Immunotherapy (5P01CA049605-33). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10700007. Licensed CC0.

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